NACHO_MOUSE
ID NACHO_MOUSE Reviewed; 167 AA.
AC Q9D328; Q9DB64;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Novel acetylcholine receptor chaperone {ECO:0000303|PubMed:26875622, ECO:0000303|PubMed:28445721, ECO:0000303|PubMed:32204458, ECO:0000303|PubMed:32783947, ECO:0000303|PubMed:33422618};
DE AltName: Full=Peroxisomal membrane protein 52;
DE Short=PMP52;
DE AltName: Full=Transmembrane protein 35A;
GN Name=Tmem35a {ECO:0000312|MGI:MGI:1914814};
GN Synonyms=Nacho {ECO:0000303|PubMed:26875622, ECO:0000303|PubMed:28445721,
GN ECO:0000303|PubMed:32204458, ECO:0000303|PubMed:32783947,
GN ECO:0000303|PubMed:33422618}, Tmem35 {ECO:0000303|PubMed:27170659};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain cortex, Cerebellum, and Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain, and Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PEROXISOMAL SUBCELLULAR LOCATION.
RC TISSUE=Kidney;
RX PubMed=17768142; DOI=10.1074/mcp.m700169-mcp200;
RA Wiese S., Gronemeyer T., Ofman R., Kunze M., Grou C.P., Almeida J.A.,
RA Eisenacher M., Stephan C., Hayen H., Schollenberger L., Korosec T.,
RA Waterham H.R., Schliebs W., Erdmann R., Berger J., Meyer H.E., Just W.,
RA Azevedo J.E., Wanders R.J., Warscheid B.;
RT "Proteomics characterization of mouse kidney peroxisomes by tandem mass
RT spectrometry and protein correlation profiling.";
RL Mol. Cell. Proteomics 6:2045-2057(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=27170659; DOI=10.1152/ajpregu.00066.2016;
RA Kennedy B.C., Dimova J.G., Dakoji S., Yuan L.L., Gewirtz J.C., Tran P.V.;
RT "Deletion of novel protein TMEM35 alters stress-related functions and
RT impairs long-term memory in mice.";
RL Am. J. Physiol. 311:R166-R178(2016).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=26875622; DOI=10.1016/j.neuron.2016.01.018;
RA Gu S., Matta J.A., Lord B., Harrington A.W., Sutton S.W., Davini W.B.,
RA Bredt D.S.;
RT "Brain alpha7 Nicotinic Acetylcholine Receptor Assembly Requires NACHO.";
RL Neuron 89:948-955(2016).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=28445721; DOI=10.1016/j.celrep.2017.04.008;
RA Matta J.A., Gu S., Davini W.B., Lord B., Siuda E.R., Harrington A.W.,
RA Bredt D.S.;
RT "NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the
RT Brain.";
RL Cell Rep. 19:688-696(2017).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=32204458; DOI=10.3390/biom10030470;
RA Deshpande A., Vinayakamoorthy R.M., Garg B.K., Thummapudi J.P., Oza G.,
RA Adhikari K., Agarwal A., Dalvi P., Iyer S., Thulasi Raman S., Ramesh V.,
RA Rameshbabu A., Rezvaya A., Sukumaran S., Swaminathan S., Tilak B., Wang Z.,
RA Tran P.V., Loring R.H.;
RT "Why Does Knocking Out NACHO, But Not RIC3, Completely Block Expression of
RT alpha7 Nicotinic Receptors in Mouse Brain?";
RL Biomolecules 10:0-0(2020).
RN [9]
RP FUNCTION, AND INTERACTION WITH RPN1; RPN2 AND CANX.
RX PubMed=32783947; DOI=10.1016/j.celrep.2020.108025;
RA Kweon H.J., Gu S., Witham E., Dhara M., Yu H., Mandon E.D., Jawhari A.,
RA Bredt D.S.;
RT "NACHO Engages N-Glycosylation ER Chaperone Pathways for alpha7 Nicotinic
RT Receptor Assembly.";
RL Cell Rep. 32:108025-108025(2020).
RN [10]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=33422618; DOI=10.1016/j.neuroscience.2020.12.027;
RA Khasabov S.G., Rogness V.M., Beeson M.B., Vulchanova-Hart L., Yuan L.L.,
RA Simone D.A., Tran P.V.;
RT "The nAChR Chaperone TMEM35a (NACHO) Contributes to the Development of
RT Hyperalgesia in Mice.";
RL Neuroscience 457:74-87(2021).
CC -!- FUNCTION: Molecular chaperone which mediates the proper assembly and
CC functional expression of the nicotinic acetylcholine receptors (nAChRs)
CC throughout the brain (PubMed:26875622, PubMed:28445721,
CC PubMed:32204458). Essential for the proper folding, assembly, function
CC and surface trafficking of alpha-7 (CHRNA7), alpha-4-beta-2, alpha-3-
CC beta-2 and alpha-3-beta-4 receptors (PubMed:26875622, PubMed:28445721,
CC PubMed:32204458). Stably associates with ribophorin-1 (RPN1) and
CC ribophorin-2 (RPN2) (components of the oligosaccharyl transferase (OST)
CC complex) and with calnexin (CANX), both of which are critical for
CC NACHO-mediated effects on CHRNA7 assembly and function
CC (PubMed:32783947). Facilitates the proper folding and assembly of
CC alpha-6-beta-2 and alpha-6-beta-2-beta-3 receptors and acts at early
CC stages of the nAChRs subunit assembly (PubMed:28445721). Promotes the
CC expression of the alpha-4(2):beta-2(3) stoichiometric form over the
CC alpha-4(3):beta-2(2) form (By similarity).
CC {ECO:0000250|UniProtKB:Q53FP2, ECO:0000269|PubMed:26875622,
CC ECO:0000269|PubMed:28445721, ECO:0000269|PubMed:32204458,
CC ECO:0000269|PubMed:32783947}.
CC -!- SUBUNIT: May interact with NGFR (By similarity). Interacts with RPN1,
CC RPN2 and CANX (PubMed:32783947). {ECO:0000250|UniProtKB:Q6JAM9,
CC ECO:0000269|PubMed:32783947}.
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane
CC {ECO:0000269|PubMed:17768142}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q6JAM9}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:28445721}; Multi-
CC pass membrane protein {ECO:0000255}. Note=Shedding may lead to a
CC soluble peptide. {ECO:0000250|UniProtKB:Q6JAM9}.
CC -!- TISSUE SPECIFICITY: Brain (at protein level) (PubMed:27170659,
CC PubMed:26875622, PubMed:28445721). Expressed in the spinal cord dorsal
CC horn (at protein level) (PubMed:33422618).
CC {ECO:0000269|PubMed:26875622, ECO:0000269|PubMed:27170659,
CC ECO:0000269|PubMed:28445721, ECO:0000269|PubMed:33422618}.
CC -!- DISRUPTION PHENOTYPE: Mice show a complete disruption of the assembly
CC and function of the neuronal acetylcholine receptor (nAChR) subunit
CC alpha-7 (CHRNA7) in the brain (PubMed:26875622, PubMed:32204458).
CC Exhibit enhanced locomotor activity, profound abnormalities in
CC spatial/working memory and a significant reduction of assembled nAChRs
CC in the brain (PubMed:28445721). Display thermal hyperalgesia and
CC mechanical allodynia accompanied by an increased number of microglia in
CC the spinal cord dorsal horn (PubMed:33422618). Exhibit elevated basal
CC serum corticosterone accompanied by increased anxiety-like behavior and
CC an impairment of long-term memory (PubMed:27170659).
CC {ECO:0000269|PubMed:26875622, ECO:0000269|PubMed:27170659,
CC ECO:0000269|PubMed:28445721, ECO:0000269|PubMed:32204458,
CC ECO:0000269|PubMed:33422618}.
CC -!- SIMILARITY: Belongs to the DoxX family. {ECO:0000305}.
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DR EMBL; AK005180; BAB23865.1; -; mRNA.
DR EMBL; AK018535; BAB31260.1; -; mRNA.
DR EMBL; AK042538; BAC31285.1; -; mRNA.
DR EMBL; AK043881; BAC31693.1; -; mRNA.
DR EMBL; BC042623; AAH42623.1; -; mRNA.
DR EMBL; BC050880; AAH50880.1; -; mRNA.
DR CCDS; CCDS30392.1; -.
DR RefSeq; NP_080515.1; NM_026239.2.
DR AlphaFoldDB; Q9D328; -.
DR STRING; 10090.ENSMUSP00000044926; -.
DR iPTMnet; Q9D328; -.
DR PhosphoSitePlus; Q9D328; -.
DR SwissPalm; Q9D328; -.
DR EPD; Q9D328; -.
DR MaxQB; Q9D328; -.
DR PaxDb; Q9D328; -.
DR PeptideAtlas; Q9D328; -.
DR PRIDE; Q9D328; -.
DR ProteomicsDB; 259226; -.
DR Antibodypedia; 28590; 32 antibodies from 15 providers.
DR DNASU; 67564; -.
DR Ensembl; ENSMUST00000037687; ENSMUSP00000044926; ENSMUSG00000033578.
DR GeneID; 67564; -.
DR KEGG; mmu:67564; -.
DR UCSC; uc009uft.1; mouse.
DR CTD; 59353; -.
DR MGI; MGI:1914814; Tmem35a.
DR VEuPathDB; HostDB:ENSMUSG00000033578; -.
DR eggNOG; ENOG502RXPR; Eukaryota.
DR GeneTree; ENSGT00940000154325; -.
DR HOGENOM; CLU_121618_0_0_1; -.
DR InParanoid; Q9D328; -.
DR OMA; ICGIIMT; -.
DR OrthoDB; 1615454at2759; -.
DR PhylomeDB; Q9D328; -.
DR TreeFam; TF300206; -.
DR BioGRID-ORCS; 67564; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Tmem35a; mouse.
DR PRO; PR:Q9D328; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q9D328; protein.
DR Bgee; ENSMUSG00000033578; Expressed in adrenal gland and 192 other tissues.
DR Genevisible; Q9D328; MM.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005778; C:peroxisomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030548; F:acetylcholine receptor regulator activity; IMP:UniProtKB.
DR GO; GO:0051131; P:chaperone-mediated protein complex assembly; IMP:UniProtKB.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IMP:UniProtKB.
DR InterPro; IPR029693; TMEM35A.
DR InterPro; IPR040399; TMEM35A/B.
DR PANTHER; PTHR13163; PTHR13163; 1.
DR PANTHER; PTHR13163:SF0; PTHR13163:SF0; 1.
PE 1: Evidence at protein level;
KW Chaperone; Cytoplasmic vesicle; Endoplasmic reticulum; Membrane;
KW Peroxisome; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..167
FT /note="Novel acetylcholine receptor chaperone"
FT /id="PRO_0000271609"
FT TOPO_DOM 1..5
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 6..26
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 27..61
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 62..82
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 83..88
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 89..109
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 110..114
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 115..132
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 133..167
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 43..54
FT /note="Interaction with NGFR"
FT /evidence="ECO:0000250|UniProtKB:Q6JAM9"
FT REGION 135..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 88
FT /note="D -> N (in Ref. 1; BAB23865)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 167 AA; 18505 MW; FC79B4CCF69335F3 CRC64;
MASPRTITIM ALSVALGLFF VFMGTIKLTP RLSKDAYSEM KRAYKSYVRA LPLLKKMGIN
SILLRKSIGA LEVACGIVMT LVPGRPKDVA NFFLLLLVLA VLFFHQLVGD PLKRYAHALV
FGILLTCRLL IARKPEDRSS EKKALPESAE EQPSLYEKAP QGKVKVS
